A5055239657- Lung Cancer Treatments and Mutations
- Biochemical and Molecular Research
- Cancer-related gene regulation
- Effects of Radiation Exposure
- Gut microbiota and health
- Malaria Research and Control
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Complement system in diseases
- Mosquito-borne diseases and control
- Cytomegalovirus and herpesvirus research
- Burn Injury Management and Outcomes
- Inflammatory Biomarkers in Disease Prognosis
- Invertebrate Immune Response Mechanisms
- Bacteriophages and microbial interactions
- Mycobacterium research and diagnosis
- Advanced biosensing and bioanalysis techniques
- Peptidase Inhibition and Analysis
- Animal Virus Infections Studies
- Climate Change and Health Impacts
- Wound Healing and Treatments
- Medical and Biological Ozone Research
- Diet and metabolism studies
- Monoclonal and Polyclonal Antibodies Research
Henry M. Jackson Foundation
2024-2025
Uniformed Services University of the Health Sciences
2023-2025
Jackson Foundation
2024
Unifor
2024
American Type Culture Collection
2020-2021
Abstract The clinical effectiveness of KRASG12C inhibitors (G12Ci) is limited both by intrinsic and acquired resistance, necessitating the development combination approaches. Here, we identified targeting proximal receptor tyrosine kinase (RTK) signaling using SOS1 inhibitor (SOS1i) BI-3406 as a strategy to improve responses G12Ci treatment. SOS1i enhanced efficacy rebound RTK/ERK overcome intrinsic/adaptive but this effect was modulated SOS2 protein levels. drug tolerant persister (DTP)...
<p>SHP2i prevents G12Ci-induced TIC outgrowth.</p>
<p>SOS1i synergizes with G12Ci under both 2D and 3D culture conditions.</p>
<p>SOS1i synergizes with G12Ci to limit MAPK pathway signaling under 2D and 3D conditions.</p>
<p>KRASG12C-mutated cell lines show universal G12Ci:SOS1i synergy in low-serum conditions.</p>
<p>G12Ci treatment increases aldehyde dehydrogenase activity in LUAD cells.</p>
<p>SOS1 and SOS2 protein abundance is stable in G12Ci DTPs.</p>
<p>KRASG12C-mutated cell lines show differential G12Ci:SOS1i synergy.</p>
<p>SOS1i synergizes with G12Ci to drive transcriptional changes regulating MAPK signaling.</p>
<p>SOS1 inhibition limits the development of acquired G12Ci resistance.</p>
<p>SOS1i prevents G12Ci-induced TIC outgrowth.</p>
<p>SOS1i synergizes with G12Ci or MEKi in ALDHhigh cells.</p>
<p>SOS2 expression determines the extent of G12Ci:SOS1i synergy.</p>
<p>G12Ci DTPs show increased CD133+ / ALDHhigh cells.</p>
<p>G12Ci DTPs show reduced sensitivity to G12Ci that is restored by SOS1i or ALDHi treatment.</p>
<div>Abstract<p>The clinical effectiveness of KRAS<sup>G12C</sup> inhibitors (G12Ci) is limited both by intrinsic and acquired resistance, necessitating the development combination approaches. Here, we identified targeting proximal receptor tyrosine kinase signaling using SOS1 inhibitor (SOS1i) BI-3406 as a strategy to improve responses G12Ci treatment. SOS1i enhanced efficacy rebound kinase/ERK overcome intrinsic/adaptive but this effect was modulated SOS2 protein...
<p>SOSi prevents MEKi-induced TIC outgrowth.</p>
<p>SOS1i shows dose-dependent inhibition of G12Ci acquired resistance.</p>
<p>G12Ci DTPs show reduced G12Ci engagement after washout.</p>
<p>KEAP1 and STK11 co-mutations alter basal ERK AKT phosphorylation.</p>
<p>KRASG12C-mutated cell lines show universal G12Ci:SOS1i synergy in the absence of SOS2.</p>
<p>SOS2 expression determines the extent of G12Ci:SOS1i synergy.</p>
<p>KRASG12C-mutated cell lines show universal G12Ci:SHP2i synergy.</p>
Several "primary atopic disorders" are linked to monogenic defects that attenuate TCR signaling, favoring T helper type 2 (TH2) cell differentiation. Patients with CARD11-associated atopy dominant interference of NF-κB signaling (CADINS) disease suffer from severe atopy, caused by germline loss-of-function/dominant interfering (LOF/DI) CARD11 variants. The scaffold enables TCR-induced activation NF-κB, mTORC1, and JNK yet the function CARD11-dependent in cells remains nebulous. Here we show...
Abstract Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease that leads to loss of motor neurons in the anterior horn spinal cord with consequent muscle atrophy. SMA results from functional deletions SMN1 gene, resulting insufficient production survival neuron (SMN) protein. It not known why lower are particularly sensitive SMN function, but it increasingly apparent extraneuronal tissues, such as cardiac and skeletal muscle, also affected by deficiency. We have previously...